Alcohol abuse (intoxication, tolerance development, physical dependency) is perhaps the most significant drug problem in America today. Alcohol has a primary effect via its actions on nerve synapses and it is probable that many of the behavioral changes associated with its abuse are due to its effects on mechanisms responsible for synaptic plasticity. Hence, the long term goal of this project is to define the mechanisms by which alcohol affects synaptic plasticity to produce intoxication, tolerance or withdrawal dependence. To attain this goal, crayfish neuromuscular junctions which exhibit much synaptic plasticity have been- developed as a model system to characterize the electrophysiological and biophysical mechanisms by which alcohol alters synaptit plasticity to produce behavioral changes. Our specific aims for this three yea: proposal are to characterize the pre- and postsynaptic mechanisms by which alcohol affects facilitation, post-tetanic potentiation, long-term potentiation, presynaptic inhibition, and postsynaptic sensitivity at neuromuscular junctions taken from control animals, from animals undergoing tolerance to chronic exposure, and from animals undergoing withdrawal dependence following chronic exposure.